Dynamic Substates of the Default Mode Network Are Associated with Mystical Experiences and Clinical Outcomes after Magnesium-Ibogaine Treatment in Veterans with Traumatic Brain Injury
This new paper examines how changes in brain network dynamics after magnesium-ibogaine treatment relate to subjective psychedelic experiences and improvements in clinical symptoms.
This new paper examines how changes in brain network dynamics after magnesium-ibogaine treatment relate to subjective psychedelic experiences and improvements in clinical symptoms.
Key Findings
Magnesium-ibogaine treatment was associated with improvements in depression, anxiety and PTSD symptoms in veterans with traumatic brain injury.
Brain imaging showed changes in the default mode network (DMN), a network involved in self-reflection, memory and the sense of self. Treatment altered how flexibly the DMN moved between different activity states.
Greater changes in DMN dynamics were linked to stronger mystical-type experiences and greater improvements in clinical symptoms.
The findings suggest psychedelic-assisted therapies may work partly by increasing brain network flexibility, potentially helping to shift rigid patterns of thought and emotional processing.
The study was observational and involved a small, specific population, so controlled clinical trials are needed to confirm these effects.
However, controlled trials are needed to confirm efficacy and establish safety. Note this is a preprint paper
Abstract
Preliminary evidence suggests that the combination of magnesium and ibogaine, an atypical psychedelic, may be a promising treatment for post-traumatic stress disorder (PTSD), opioid use disorder, and traumatic brain injury (TBI). The “mystical” experience elicited by ibogaine, which is characterized by feelings of awe, selflessness, and transcendence, is correlated with improvements in PTSD symptoms. Mystical experiences with other psychedelics are associated with acute decreases in the activity and connectivity of the default mode network (DMN), which mediates self-related cognition. However, the dynamic effects of ibogaine on the DMN have not yet been studied. At baseline, immediately (3-4 days) after ibogaine, and one month after ibogaine, we acquired resting-state functional magnetic resonance imaging data in an open-label, observational trial of magnesium-ibogaine treatment for 30 U.S. veterans with TBI.
Magnesium-ibogaine did not significantly alter static DMN connectivity at either the immediate-post or one-month timepoint. Since static measures cannot capture time-evolving changes in connectivity, we next used Hidden Markov Models (HMM) to measure the post-acute dynamics of DMN activity. Magnesium-ibogaine was associated with significant, sustained decreases in the switching rate (i.e., increases in the duration of) a dynamic DMN substate, which was significantly correlated with the mean score on the Revised Mystical Experience Questionnaire and clinical improvements at one month-post treatment.
This DMN substate exhibited a lateral-medial spatial gradient, which was significantly associated with a gradient of externally oriented (i.e., directed to the environment) to internally oriented (i.e., self-related) perception and cognition. Taken together, our results indicate that magnesium-ibogaine alters specific dynamic substates of the DMN, which correlate with its subjective and therapeutic effects.
Kenneth Shinozuka, Clayton Olash, Tracy Han, Azeezat Azeez, Malvika Sridhar, Andrew D. Geoly, Catherine Daye, Saron Hunegnaw, Kirsten N. Cherian, Jackob N. Keynan, Randi E. Brown, Derrick M. Buchanan, John P. Coetzee, Ian H. Kratter, Raag D. Airan, Martijn Arns, Maheen M. Adamson, Manish Saggar, Cammie Rolle Dynamic Substates of the Default Mode Network Are Associated with Mystical Experiences and Clinical Outcomes after Magnesium-Ibogaine Treatment in Veterans with Traumatic Brain Injury medRxiv 2026.07.20.26358512; doi: https://doi.org/10.64898/2026.07.20.26358512 Read Paper
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